This proposal requests support for a Keystone Symposia meeting entitled Synapses and Circuits: From Formation to Disease, organized by Tony Koleske, Hollis T. Cline, Stefan Herlitze and Linda Van Aelst, which will be held in Steamboat Springs, Colorado from April 1 - 6, 2012. A fundamental goal of neuroscience is to understand the molecular, cellular, and activity-based mechanisms that control the formation and maintenance of neural circuits and determine how these mechanisms become compromised in neurodevelopmental, psychiatric and neurodegenerative disorders. Over the past two decades, molecular neuroscientists have identified key molecules and mechanisms that underlie synapse development, activity, and stability. Meanwhile, the study of neuronal circuits has been revolutionized by new methods to visualize and map circuits in living animals, as well as the development of approaches to control neuronal activity using optical approaches (so called optogenetics). Finally, disease researchers have identified genes associated with neurodevelopmental and psychiatric disorders and neurodegenerative diseases. Animal models of these diseases are proving useful to understand how dysfunction of affected genes and proteins contributes to disease pathology. Although these fields are working on the same processes, no small highly interactive meeting brings these three groups together. The Keystone Symposia meeting on Synapses and Circuits: From Formation to Disease will address this need by bringing together leaders working on synapse development and function, circuit structure and function, and the study of brain disease. We anticipate that mutually beneficial insights will emerge from discussions at this meeting. PUBLIC HEALTH RELEVANCE: Alterations in synaptic function, neural circuit connectivity, and neural network are hallmarks of neurodevelopmental disorders such as autism and mental retardation, and psychiatric disorders such as depression and schizophrenia. Elucidating the mechanisms that control synapse and circuit formation, stability, and function and how they are altered in developmental disorders and disease states is a fundamental problem in modern neuroscience. The 2012 Keystone Symposia meeting on Synapses and Circuits: From Formation to Disease aims to advance the understanding of the molecular and cellular mechanisms that control the formation, maintenance, and plasticity of neural circuits, as well as determine how these mechanisms become compromised in neurodevelopmental, psychiatric and neurodegenerative disorders. Disclaimer: Please note that the following critiques were prepared by the reviewers prior to the Study Section meeting and are provided in an essentially unedited form. While there is opportunity for the reviewers to update or revise their written evaluation, based upon the group's discussion, there is no guarantee that individual critiques have been updated subsequent to the discussion at the meeting. Therefore, the critiques may not fully reflect the final opinions of th individual reviewers at the close of group discussion or the final majority opinion of the group. Thus the Resume and Summary of Discussion is the final word on what the reviewers actually considered critical at the meeting.